Maarten Altelaar is associate professor at the Department of Pharmaceutical Sciences of the Utrecht University. The research in his group focuses on the development and implementation of innovative mass spectrometric methods for the more efficient and detailed characterization of proteins, protein complexes and their post-translational modifications (PTMs) in relation to their biological function in health and disease, Main emphasis is on the improvement of sensitivity, specificity and throughput of proteomics technology for the investigation of cellular differentiation and signalling networks in cancer proteomics, stem cell differentiation and neuronal development. As such his lab has pioneered label free phosphopeptide quantification using Ti4+-IMAC affinity beads in combination with targeted mass spectrometry (SRM) to monitor pathway specific phosphorylation dynamics. To further improve identification rates of such PTMs as well as of other proteolytic peptides that are difficult to tackle with conventional MS fragmentation technologies, he has been actively involved in the development of the electron transfer dissociation (ETD) as alternative fragmentation technology. These developments combined now allow increased depth of coverage for proteome and phosphoproteome wide analysis. More recently, his group has begun implementing multi-omics approaches to understand system-wide biological responses to perturbations in the light of drug sensitivity and resistance. In 2013 he received a VIDI grant to work on proteome wide crosstalk mechanisms in cancer signalling and drug resistance. Besides personal grants as PI and co-PI, he is involved in large consortia such as the Netherlands Proteomics Centre, Proteins@work and PrimeXS. He is currently the treasurer of the Dutch Society for Mass Spectrometry, organizing two scientific meetings yearly. Further, he developed and taught several lectures revolving around different facets of mass spectrometry and proteomics.

The Institute for Chemical Immunlogy is an NWO Gravitation project coordinator by Leiden University. It will define and exploit a new field termed chemical immunology and train a novel generation of interdisciplinary scientists. It aims to promote academic excellence; with economic and clinical translation of new treatment options for a large population of patients that currently only have limited treatment options.

Proteins At Work is a project in the NWO National Roadmap for Large-Scale Research Facilities programme which encourages the establishment or improvement of large research facilities with which the Netherlands can assume an important position internationally. Proteins At Work will make high-level technology, equipment and expertise for studying proteins in cells and tissues available to the biological and biomedical researchers in the Netherlands. The Proteins At Work programme is a collaboration between Utrecht University, the UMC Utrecht, the Hubrecht Institute, the Erasmus MC Rotterdam and the Netherlands Cancer Institute and is coordinated by prof. dr. Albert Heck.

Understanding how living systems function is one of the fundamental goals in bio-molecular science. The molecular machinery controlling these functions is comprised of a highly complex collection of distinct molecules that act in coordinate fashion. The global analysis of proteins, representing the key functional entities in the cell, forms arguably the basis for understanding how cells function. However, gathering information at the proteome level poses a tough analytical challenge, when comparing it to data collection at the genome and transcriptome level. This is mainly caused by its highly multilayered character with alternative splicing and diverse posttranslational modifications (PTMs), further amplified by the dynamic interplay between PTMs and proteins in complexes and signaling networks. This interplay leads to so called ‘crosstalk’ mechanisms, where, if one node in the complex machinery is affected, other nodes respond either compensatory or inhibitory. Uncovering this extreme complexity is one of the challenges that drives proteomics research, which heavily relies on mass spectrometry based protein sequencing. With the here proposed developments in methodology, sample preparation and computational analysis, I will contribute to overcoming this challenge. I will develop and implement a unique combination of high resolution quantitative proteomics tools that allow the analysis of this dynamic proteome at system wide scales, while maintaining physiologically relevant conditions. The tools will focus on sensitivity, crucial when dealing with limited sample amounts, comprehensiveness, to tackle (PTM) crosstalk, and throughput, important when targeting many different sample types. As model system I will perturb the melanoma cancer proteome, using physiological relevant slow dividing cell lines, tumour tissue and patient derived xenografts, and monitor its response in the face of PTM expression, network rewiring and drug resistance. As many types of cancer are lacking proper treatment caused by limited understanding of the molecular mechanisms involved, the developed technology will be widely applicable.

Completed projects

Project:

PRIME-XS01.02.2011to31.01.2015

General project description

PRIME-XSprovides European Union funded access to an infrastructure of state-of-the-art proteomics technology to the biological and biomedical research community in Europe. European researchers who would like to use proteomics technology for their research can apply with a research proposal on this website. PRIME-XS is a consortium of twelve partners, all leading in the field of proteomics. In addition to providing access, we develop new technologies to better aid the research community in answering current day scientific questions, and organize courses and meetings.